A First-in-human Trial of GEN3017 in Hodgkin Lymphoma and Non-Hodgkin Lymphoma

Phase 2TerminatedNCT06018129

Genmab9 enrolled

Overview

The purpose of this trial is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of GEN3017 as a monotherapy in participants with relapsed or refractory (R/R) CD30-expressing lymphomas. GEN3017 will be administered via subcutaneous injections. All participants will receive active drug; no one will be given placebo.

This multicenter trial will be conducted in 2 parts: Dose Escalation (phase 1) and Expansion (phase 2a). The Dose Escalation Part (phase 1) of the trial will evaluate dose-limiting toxicities (DLTs) to determine the recommended phase 2 dose (RP2D), and if reached, the maximum tolerated dose (MTD) for R/R CD30+ classical Hodgkin lymphoma (cHL) and R/R CD30+ T-cell lymphoma (TCL), respectively. The Expansion Part (phase 2a) will evaluate the anti-tumor activity of GEN3017 at the RP2D and selected dosage(s) will be assessed together with safety, immunogenicity, pharmacokinetics, and pharmacodynamics in R/R CD30+ cHL participants (including adults; and adolescent and young adults) and in participants with selected R/R CD30+ TCL subtypes (adults only).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Classical Hodgkin Lymphoma Non-Hodgkin Lymphoma

Interventions

GEN3017BIOLOGICAL

Subcutaneous injection

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: Dose Escalation Part: 1. Must be at least 18 years of age. For participants in the R/R cHL Cohort in the United States (US) and Australia, must be at least 16 years of age. 2. Histologically confirmed R/R cHL or R/R TCL. 3. Participants must have at least 1 measurable lesion by fluorodeoxyglucose-positron emission tomography (FDG-PET) scan demonstrating positive lesion compatible with computed tomography (CT)- or magnetic resonance imaging (MRI)-defined anatomical tumor sites and a CT scan (or MRI) with involvement of ≥1 measurable nodal lesion and/or ≥1 measurable extranodal lesion. 4. Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1 for participants 18 years of age and above. For participants ≥16 and \<18 years of age (US and Australia only), Karnofsky score of \>60% per Karnofsky performance scale. 5. Confirmed CD30-positivity in tumor biopsy prior to the first dose of GEN3017. 6. R/R cHL Cohort: * Must have relapsed or progressive cHL after receiving at least 2 or 3 prior lines of therapy; OR * Refractory to the second line of therapy. Key Exclusion Criteria: 1. Primary central nervous system (CNS) tumor or known CNS involvement. 2. Received prior investigational CD30-targeting therapy (except brentuximab vedotin). 3. Autologous hematopoietic stem cell transplant (HSCT) within 60 days (applies to both cHL and TCL). Allogeneic HSCT within 90 days (applies to cHL) prior to the first dose of GEN3017. 4. Chemotherapy within 2 weeks or major surgery within 4 weeks prior to the first dose of GEN3017. 5. Curative radiotherapy within 4 weeks or palliative radiotherapy within 2 weeks prior to the first dose of GEN3017. 6. Treatment with an investigational drug within 4 weeks or 5 half-lives of the drug, whichever is shorter prior to the first dose of GEN3017 or currently receiving any other investigational agents. 7. Prior treatment with live, attenuated vaccines within 30 days prior to the first dose of GEN3017. 8. Receiving immunosuppressive drugs or systemic corticosteroids such as prednisone at doses \>25 milligrams (mg) daily or its equivalent within 14 days prior to the first dose of GEN3017. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (4)

City of Hope Helford Clinical Research Hospital

Duarte, California, United States

Washington University School of Medicine

St Louis, Missouri, United States

MD Anderson Cancer Center

Houston, Texas, United States

Peter MacCallum Cancer Institute trading as Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Outcomes

Primary Outcomes

Dose Escalation Part: Number of Participants With Dose-Limiting Toxicities (DLTs)

A DLT was defined as any of the following toxicities except those that were clearly due to the underlying disease or extraneous cause: all Grade 5 toxicities, hematological toxicities (Grade 4 neutropenia, Grade 3 and Grade 4 febrile neutropenia lasting \>2 days, Grade 4 thrombocytopenia of any duration with clinically significant bleeding or ≥ Grade 3 thrombocytopenia requiring platelet transfusion, Grade 4 anemia), non-hematological toxicities (Grade 4 cytokine release syndrome \[CRS\] per American Society for Transplantation and Cellular Therapy \[ASTCT\] criteria or Grade 3 unresolved to ≤ Grade 2 within 48 hours following adequate intervention, Grade 4 immune effector cell-associated neurotoxicity syndrome \[ICANS\] according to ASTCT criteria or Grade 3 unresolved to ≤ Grade 2 within 48 hours following adequate intervention, tumor lysis syndrome \[TLS\] Grade 4 or Grade 3 unresolved within 5 days, any ≥ Grade 3 \[severe or life-threatening\] non-hematological toxicities \[with exceptions\]).

Time frame: 21 days

Dose Escalation Part: Number of Participants With Adverse Events (AEs)

An AE was defined as any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

Time frame: Up to approximately 1 year 2 months

Secondary Outcomes

Dose Escalation Part: Maximum (Peak) Plasma Concentration (Cmax) of GEN3017

Venous blood samples were collected for analyzing concentrations of GEN3017.

Time frame: Day 1 and Day 8

Dose Escalation Part: Time to Reach Cmax (Tmax) of GEN3017

Venous blood samples were collected for analyzing concentrations of GEN3017.

Data from ClinicalTrials.gov

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